Gastric mucosal damage in the course of acute liver failure: which pharmacological options?

Abstract The aim of the present study was to gain further insights into the pathophysiological mechanisms of acute gastric injury during the course of acute hepatic failure (AHF), with a particular view to the search for a therapeutic approach. D-galactosamine HCl (Ga-HCl)-induced AHF model was reproduced in male albino rabbits. Four groups of rabbits were considered: (1) Ga-HCl; (2) Ga-HCl plus 15 μg/kg misoprostol q.i.d. perorally; (3) Ga-HCl plus a 24-h i.v. infusion of 1 mg/kg/h ranitidine; (4) Ga-HCl plus a 24-h i.v. infusion of 0.4 mg/kg/h omeprazole. All rabbits developed a full-blown AHF, irrespective of the treatment. Group 1 rabbits had an overall 84% incidence of hemorrhagic lesions, the gastric body and fundus being most affected, whereas in groups 2, 3 and 4 the incidence was around 25%. Gastric pH greatly decreased in group 1 and 2 but not in group 3 and 4. Group A showed a marked drop in gastric mucosal blood flow and hemoglobin oxygen saturation together with a decreased mucosal hexosamine content associated with an enhanced glucosaminidase activity. These phenomena were prevented by misoprostol and omeprazole but not by ranitidine. Only misoprostol prevented the decrease of gastric mucosal PGE 2 content observed in AHF. These data suggest that during the course of AHF, drugs affecting the cytoprotective mechanisms besides gastric acid secretion per se are the most suitable therapeutic options to counteract the underlying abnormalities taking place in this condition.